Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery

Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process(1). Activation of PLK1 requires phosphorylation of a conserved threonine residue ( Thr 210) in the T- loop of the PLK1 kinase domain, but the kinase responsible for this has not yet been affirmatively identified(2-6). Here we show that in human cells PLK1 activation occurs several hours before entry into mitosis, and requires aurora A ( AURKA, also known as STK6)- dependent phosphorylation of Thr 210. We find that aurora A can directly phosphorylate PLK1 on Thr 210, and that activity of aurora A towards PLK1 is greatly enhanced by Bora ( also known as C13orf34 and FLJ22624), a known cofactor for aurora A ( ref. 7). We show that Bora/ aurora- A- dependent phosphorylation is a prerequisite for PLK1 to promote mitotic entry after a checkpoint- dependent arrest. Importantly, expression of a PLK1- T210D phospho- mimicking mutant partially overcomes the requirement for aurora A in checkpoint recovery. Taken together, these data demonstrate that the initial activation of PLK1 is a primary function of aurora A.